Variant rs6560891 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_170682.4(P2RX2):c.636-13G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,613,580 control chromosomes in the GnomAD database, including 304,891 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34539 hom., cov: 33)

Exomes 𝑓: 0.61 ( 270352 hom. )

Consequence

P2RX2
NM_170682.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.521

Variant links:

Genes affected

P2RX2 (HGNC:15459): (purinergic receptor P2X 2) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel. Binding to ATP mediates synaptic transmission between neurons and from neurons to smooth muscle. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Aug 2013]

P2RX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-132620432-G-A is Benign according to our data. Variant chr12-132620432-G-A is described in ClinVar as [Benign]. Clinvar id is 226986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX2	NM_170682.4 linkuse as main transcript	c.636-13G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000643471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX2	ENST00000643471.2 linkuse as main transcript	c.636-13G>A		splice_polypyrimidine_tract_variant, intron_variant			NM_170682.4	A2	Q9UBL9-1

Frequencies

GnomAD3 genomes

AF:

0.666

AC:

101185

AN:

151976

Hom.:

34505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.799

Gnomad AMI

AF:

0.570

Gnomad AMR

AF:

0.733

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.803

Gnomad SAS

AF:

0.606

Gnomad FIN

AF:

0.560

Gnomad MID

AF:

0.617

Gnomad NFE

AF:

0.590

Gnomad OTH

AF:

0.637

GnomAD3 exomes

AF:

0.643

AC:

161399

AN:

251172

Hom.:

53248

AF XY:

0.629

AC XY:

85485

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.799

Gnomad AMR exome

AF:

0.794

Gnomad ASJ exome

AF:

0.508

Gnomad EAS exome

AF:

0.812

Gnomad SAS exome

AF:

0.599

Gnomad FIN exome

AF:

0.560

Gnomad NFE exome

AF:

0.587

Gnomad OTH exome

AF:

0.624

GnomAD4 exome

AF:

0.605

AC:

884394

AN:

1461486

Hom.:

270352

Cov.:

AF XY:

0.603

AC XY:

438748

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.797

Gnomad4 AMR exome

AF:

0.784

Gnomad4 ASJ exome

AF:

0.507

Gnomad4 EAS exome

AF:

0.805

Gnomad4 SAS exome

AF:

0.594

Gnomad4 FIN exome

AF:

0.558

Gnomad4 NFE exome

AF:

0.590

Gnomad4 OTH exome

AF:

0.611

GnomAD4 genome

AF:

0.666

AC:

101273

AN:

152094

Hom.:

34539

Cov.:

AF XY:

0.665

AC XY:

49480

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.799

Gnomad4 AMR

AF:

0.734

Gnomad4 ASJ

AF:

0.505

Gnomad4 EAS

AF:

0.803

Gnomad4 SAS

AF:

0.606

Gnomad4 FIN

AF:

0.560

Gnomad4 NFE

AF:

0.590

Gnomad4 OTH

AF:

0.640

Alfa

AF:

0.600

Hom.:

32810

Bravo

AF:

0.685

Asia WGS

AF:

0.692

AC:

2404

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 24, 2014

636-13G>A in intron 6 of P2RX2: This variant is not expected to have clinical si gnificance because it has been identified in 41.4% (3564/8600) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs6560891). -

Autosomal dominant nonsyndromic hearing loss 41

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.7

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over